Perfect Day “teaches” microflora - safe, commonly used microorganisms that have been used to make food and enzymes for decades - to make whey protein. The resulting protein powder is analyzed to ensure it’s consistent, efficient, and safe.

Precision Fermentation Comes Into its Own

Feb. 7, 2024
It took 40-plus-years for this food and pharmaceutical technology to become an overnight sensation for product development.

Humans have used rennet to curdle milk in cheese-making for millennia. Chymosin is the critical enzyme in rennet. When a shortage of rennet developed in the 1980s to the 1990s, researchers inserted chymosin-producing genes like those possessed by calves into microorganisms. As a result, some 70-90% of the chymosin used in cheese manufacturing today is produced by precision fermentation.

RethinkX asserts it coined the term precision fermentation in its 2019 Food & Agriculture Report. Microorganisms such as yeast, algae, bacteria or fungi are given the genetic code to ferment substrates such as plant sugars (i.e., their foodstuff) into specific desired organic ingredients. Fermentation occurs in bioreactors under tightly controlled conditions. The microorganisms are eventually removed and are not present in the final product.

The purity of the targeted ingredient and the absence of cells or cell components in the final product in part differentiates precision fermentation from “biomass fermentation,” another emerging fermentation technology. “In biomass fermentation, the microorganisms that reproduce through this process are themselves ingredients for alternative proteins,” explains the Good Food Institute.

Precision fermentation has been invaluable to human health through drugs like human insulin, human growth hormone and the hepatitis B vaccine. The technology plays a role in biologics that treat conditions including anemia, AIDS, hepatitis C, multiple sclerosis and certain cancers.

In foods, renewed interest in precision fermentation is due to technological advances in producing functional ingredients with high yields, relative purity and a range of promised environmental and social benefits. Following are some representative cases.

An Aug. 30, 2023, blog from the Precision Fermentation Alliance relays statistics from an ISO-compliant life cycle analysis by PFA member Perfect Day. It found that precision fermentation-derived whey uses up to 99% less blue water, generates up to 97% fewer greenhouse emissions and uses up to 60% less non-renewable energy.

In another example, the colorant betanin is present at about 0.2% wet weight in red beetroots. “This extraction is incredibly wasteful in land use, processing costs and vegetable waste,” notes researchers at the Novo Nordisk Foundation Center for Biosustainability at the Technical University of Denmark. Precision fermentation enables the yeast yarrowia lipolytica to produce betanin and its isomer that require significantly less land, energy and resources than the extraction of betanin from beetroot.

Rare ingredients with unique properties that would not be commercially viable otherwise have been developed. Sweegen uses precision fermentation to produce the unusually stable, high-purity sweetener brazzein.

Precision fermentation may best be known for its ability to generate proteins. TurtleTree uses it to produce LF+, a bioactive protein lactoferrin. It occurs at high levels in human colostrum (about 7 g/L) and mature milk (about 1 g/L), but in cow’s milk, it is only about 1.5 mg/L in colostrum and 0.5 mg/L in mature milk. Its beneficial properties include “antibacterial, antiviral, antifungal and antiparasitic, as well as immunomodulatory, anti-inflammatory and anticancer properties...”

Also under development or commercially available for some time are amino acids, peptides, enzymes and other proteins, vitamin B12, lipids, carbohydrates, flavorings such as vanillin (the key flavor molecule in vanilla), other colorants, antioxidants, preservatives, probiotics and citric acid, all produced by precision fermentation.

With such advantages and benefits, precision fermentation has found a home beyond cheese manufacturers to produce products such as frozen dairy alternative desserts, cake mixes and sports nutrition products. The producers of the food ingredients for these consumer goods are some of the strongest advocates.

“We chose to create protein from fermentation because it unlocks a truly no-compromise way to continue to enjoy the foods we love,” says Nikki Briggs, vice president of corporate communications for Perfect Day. “Precision fermentation allows us to produce the same protein found in milk, enabling planet-positive impact without compromising what we love about dairy: its taste, texture, nutrition and functionality.”

Benefits, growth, but headwinds

Allied Market Research’s report “Precision Fermentation Market Research, 2031” predicts the global precision fermentation market value will grow from $1.3 billion in 2021 to an estimated $34.9 billion by 2031. That’s a compound annual growth rate of 40.5%.

However, operational headwinds are many. Regulatory approvals (to help ensure product safety, such as allergens in non-typical food formats), technical feasibility, high scale-up cost, production and commercialization, and substrate raw material availability are often mentioned as hurdles. Ethical and consumer concerns also exist. And much R&D must still be conducted before this technology reaches its full potential.

“Developing protein-based animal analogue products from non-animal protein sources is complicated,” says René Floris, division manager food for Nizo, a Dutch contract research company. But utilizing proteins from precision fermentation has advantages over traditional plant-based proteins.

For example, creating a dairy food analogue based on soy or other plant proteins requires much processing to modify the plant protein, and considerable work also goes into the formulation and production of the consumer product in which it’s used. Traditional dairy proteins differ significantly from plant proteins regarding nutritional value, taste and flavor, physiochemical properties and potential food safety, such as allergenicity or intolerance.

In contrast, a casein protein molecule created through precision fermentation from cow DNA would be identical in amino acid profile, attached sugar moieties, etc., to that obtained directly from a cow. Thus, its properties would also be expected to be identical or nearly identical, says Floris.

However, there are two main challenges in moving from a precision-fermentation-derived protein molecule to a consumer product on the shelf, says Emma Teuling, protein expert at Nizo. First, there is a very high cost to mass-produce the protein. Expensive media and large fermenters are needed, plus there are processing expenses to purify the desired protein molecule from the source organism.

Second, milk, yogurt, cheese and other traditional dairy foods are complex systems with many components that occur in specific ratios. Cow’s milk has more than 25 types of protein as well as carbohydrates, lipids, minerals, and so on. For a dairy analogue product to approach a traditional dairy food's sensory, nutritional and physiochemical properties, considerable resources are required from talented product developers, and additional product processing is needed.

Development cost reduction

During R&D, futile lines of investigation should be eliminated as soon as possible for increased efficiency and decreased costs. Early testing of a very costly protein, which is usually only available in minute amounts from precision fermentation, is essential, says Floris.

“You want to ensure you’re developing an ingredient with the proper functionality,” adds Teuling. Does the protein have the desired physiochemical properties, such as water solubility or the ability to gel? When the protein is used in an application, what will its nutritional properties, flavor, texture, and nutritional value be? The analysis of an application is typically costly since a relatively large sample size is needed.

Nizo has developed micro-food models that can be of great assistance. For example, Nizo’s micro cheese model can test cheeses in amounts as little as just over 1ml. Various types of cheese can be screened for textures, flavors and other attributes using tiny amounts. “We have validated the use of micro food models in cheese and yogurt,” says Teuling.

Adds Floris, “We see that food companies interested in developing proteins based on precision fermentation are eager to use validated food models to screen and test ingredients on a small scale early in the development process to increase development speed and decrease costs. This is especially true since models of relevant big markets, such as cheese and yogurt, are available.”

Informed consumers & new technologies

A March 2, 2022, article titled “What Consumers Should Ask About Precision Fermentation” in Forbes lists further considerations in adopting this, or indeed any, innovative technology. They involve food safety oversight on substrate contamination and nutrient quality of finished products (compared to traditional counterparts). What is the effect on social factors, such as consumer prices and inequalities already present in our current food system (e.g., waste disposal)? Who owns the intellectual property? For example, what if there is sole ownership of crucial components — whether foods, pharmaceuticals or other organic compounds in limited supply?

How sustainable is this technology? What are the waste products and resources consumed in terms of energy and materials for massive production facilities? Should life cycle assessment of sustainability be compared to traditional concentrated animal feedlot operations or the range of other emerging agricultural processes like regenerative agriculture to agroecology?

Consumers remain cautious regarding what they put in their bodies, Shelley Balanko, senior vice president at the Hartman Group, said at the 2023 Clean Label Conference. But consumers' resistance to food science and technology may be softening as awareness of our food system's challenges grows.

Some 64% of respondents in a Hartman report, "Food & Technology 2023," said they were "open to trying foods grown, raised or processed using new developments in science, biology, and technology," a 6% increase from Hartman's 2019 Food & Technology report.

Balanko advises that the food industry must demonstrate the purpose and humanity of unfamiliar, disruptive food production technologies to increase consumer acceptance. Consumers need to feel empowered by informed choices. Last, companies should work to ensure the new technology provides value, not just flash.

As with all products, "Consumers will judge tech-forward foods on the value they bring to their lives," she concludes.

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